Ingo Slottosch

Preoperative statin therapy in cardiac surgery: a meta-analysis of 90 000 patients †

The objective of this systematic literature review with meta-analysis was to determine the strength of evidence for a preoperative statin on the reduction of adverse postoperative outcomes in patients undergoing cardiac surgery. Randomized controlled (RCT) and observational trials were searched in online databases that reported about the effects of preoperative statin therapy on major adverse clinical outcomes after cardiac surgery. Analysed outcomes included early all-cause mortality, myocardial infarction, atrial fibrillation (AF), stroke and renal failure using a priori-defined criteria. Effect estimates were calculated and are given as odds ratio (OR) with 95% confidence intervals (95% CI) using fixed- or random-effect models. Literature search of all major databases retrieved 2371 studies. After screening, a total of 54 trials were identified (12 RCT, 42 observational) that reported outcomes of 91 491 cardiac surgery patients with (n = 46 614; 51%) or without (n = 44 877; 49%) preoperative statin therapy. Preoperative statin use resulted in a 0.9% absolute risk (2.6 vs 3.5%) and a 31% odds reduction for early all-cause mortality (OR 0.69; 95% CI 0.59-0.81; P < 0.0001). In addition, statin treatment before surgery was associated with a substantial reduction (P < 0.01) in the postoperative end-points AF (OR 0.71; 95% CI 0.61-0.82), new-onset AF (OR 0.68; 95% CI 0.54-0.85), stroke (OR 0.83; 95% CI 0.74-0.93), stay on intensive care unit (weighted mean difference [WMD] -0.14; 95% CI -0.23 to -0.03; P < 0.01) and in-hospital stay (WMD -0.57; 95% CI -0.76 to -0.38; P < 0.01). No statistical differences were found between groups with regard to myocardial infarction or renal failure. In conclusion, the current systematic review strengthens the evidence that preoperative statin therapy extends substantial clinical benefit to early postoperative outcomes in cardiac surgery patients.

Current evidence of coronary artery bypass grafting off-pump versus on-pump: a systematic review with meta-analysis of over 16 900 patients investigated in randomized controlled trials†.

In the present systematic review with meta-analysis, we sought to determine the current strength of evidence for or against off-pump and on-pump coronary artery bypass grafting (CABG) with regard to hard clinical end-points, graft patency and cost-effectiveness. We performed a meta-analysis of only randomized controlled trials (RCT) which reported at least one of the desired end-points including: (i) major adverse cardiac and cerebrovascular events (MACCE), (ii) all-cause mortality, (iii) myocardial infarction, (iv) cerebrovascular accident, (v) repeat revascularization, (vi) graft patency and (vii) cost-effectiveness. The pooled treatment effects [odds ratio (OR) or weighted mean difference, 95% confidence intervals (95% CIs)] were assessed using a fixed or random effects model. A total of 16 904 patients from 51 studies were identified after literature search of the major databases using a predefined keyword list. The incidence of MACCE did not differ between the groups, neither during the first 30 days (OR: 0.93; 95% CI: 0.82-1.04) nor for the longest available follow-up (OR: 1.01; 95% CI: 0.92-1.12). While the incidence of mid-term graft failure (OR: 1.37; 95% CI: 1.09-1.72) and the need for repeat revascularization (OR: 1.55; 95% CI: 1.33-1.80) was increased after off-pump surgery, on-pump surgery was associated with an increased occurrence of stroke (OR: 0.74; 95% CI: 0.58-0.95), renal impairment (OR: 0.79; 95% CI: 0.71-0.89) and mediastinitis (OR: 0.44; 95% CI: 0.31-0.62). There was no difference with regard to hard clinical end-points between on- or off-pump surgery, including myocardial infarction or mortality. The present systematic review emphasizes that both off- and on-pump surgery provide excellent and comparable results in patients requiring surgical revascularization. The choice for either strategy should take into account the individual patient profile (comorbidities, life expectancy, etc.) and importantly, the surgeons experience in performing on- or off-pump CABG in their routine practice.

Impact of prior percutaneous coronary intervention on the outcome of coronary artery bypass surgery: A multicenter analysis

OBJECTIVES Do prior percutaneous coronary interventions adversely affect the outcome of subsequent coronary artery bypass grafting? We investigated this effect on a multicenter basis. METHODS Eight cardiac surgical centers provided outcome data of 37,140 consecutive patients who underwent isolated first-time coronary bypass grafting between January 2000 and December 2005. Twenty-two patient characteristics and outcome variables were retrieved. Three groups of patients were analysed for in-hospital mortality and in-hospital major adverse cardiac events: patients without a previous percutaneous coronary intervention, with 1 previous intervention, and with 2 or more previous percutaneous coronary interventions before bypass grafting. A total of 29,928 patients with complete information for prior percutaneous coronary intervention underwent final analysis. Unadjusted univariate and risk-adjusted multivariate logistic regression analysis as well as computed propensity score matching were performed, based on 14 major risk factors to correct for and minimize selection bias. RESULTS A total of 10.3% of patients had 1 previous percutaneous coronary intervention, and 3.7% of patients had 2 or more previous interventions. Risk-adjusted multivariate logistic regression analysis revealed a significant association of 2 or more previous percutaneous coronary interventions with in-hospital mortality (odds ratio [OR], 2.0; confidence interval [CI], 1.4-3.0; P = .0005) and major adverse cardiac events (OR, 1.5; CI, 1.2-1.9; P = .0013). After propensity score matching, conditional logistic regression analysis confirmed the results of adjusted analysis. A history of 2 or more previous percutaneous coronary interventions was significantly associated with in-hospital mortality (OR, 1.9; CI, 1.3-2.7; P = .0016) and major adverse cardiac events (OR, 1.5; CI, 1.2-1.9; P = .0019). CONCLUSIONS Multicenter analysis confirms that a history of multiple previous percutaneous coronary interventions increases in-hospital mortality and the incidence of major adverse cardiac events after subsequent coronary artery bypass grafting. Critical discussion of the treatment strategy in these patients is warranted.

Outcomes after peripheral extracorporeal membrane oxygenation therapy for postcardiotomy cardiogenic shock: a single-center experience

BACKGROUND We assessed the short-term outcomes and predictors of 30-d mortality in patients requiring temporary, peripheral extracorporeal membrane oxygenation (ECMO) for postcardiotomy cardiac failure. METHODS The data were retrospectively obtained using our institutional patient database. All patients who had received peripheral ECMO support after surgery for acquired heart disease from 2006 to 2010 were included in the present study. The demographic and perioperative variables of the 30-d survivors and nonsurvivors were compared using the chi-square and t-test, and multivariate logistic regression analysis was performed to identify the predictors of 30-d all-cause mortality. RESULTS A total of 77 patients with a mean age of 60 ± 13 years were included in the present analysis. Successful weaning from peripheral ECMO was achieved in 62% after 79 ± 57 h of ECMO support. The overall 30-d mortality rate was 70%, and mortality was reduced to 52% in the patients in whom ECMO support could be weaned successfully. Age (per year) at ECMO implantation was the only independent preoperative predictor of 30-d mortality (odds ratio 1.09, 95% confidence interval 1.03-1.15; P = 0.003). In addition, greater lactate levels after 24 h of ECMO therapy, a longer duration of ECMO support, and the presence of any ECMO-related or gastrointestinal complications were independent predictive factors for 30-d mortality (P < 0.05). CONCLUSIONS ECMO therapy provides a valuable therapeutic strategy for postcardiotomy myocardial failure but is still limited by high complication rates with fewer than 30% of patients discharged from the hospital. Patient age appears to be an essential preoperative predictor for mortality, and the blood lactate level is a relevant marker for the assessment of efficient ECMO support.

Meta-Analysis of Patients Taking Statins Before Revascularization and Aortic Valve Surgery

Statin intake before cardiac surgery is associated with favorable outcomes. We sought to analyze the evidence for statin pretreatment before isolated coronary artery bypass graft surgery and aortic valve replacement surgery. In this meta-analysis, we demonstrate beneficial results for the endpoints mortality, stroke, atrial fibrillation, and length of stay in hospital in 36,053 statin-pretreated coronary artery bypass graft surgery patients compared with control subjects retrieved from 32 studies, but fail to detect relevant advantages through preoperative statin therapy for 3,091 patients undergoing aortic valve replacement from four trials. Strict adherence to guidelines recommending statin treatment before CABG surgery is therefore mandatory.

Rosuvastatin reloading before cardiac surgery with cardiopulmonary bypass.

Background/Purpose: Recent evidence suggests that statin-mediated cardioprotection after chronic statin therapy decreases over time and can be reactivated by preprocedural high-dose statin reloading therapy. We tested in a porcine cardiopulmonary bypass (CPB) model whether statin-related cardioprotection is further enhanced by a preoperative rosuvastatin reloading therapy. Methods: Control (n = 6), rosuvastatin-pretreated (n = 6; 20 mg/day for 7 days p.o.) and rosuvastatin-reloaded (n = 6; p.o. treatment plus 0.10 mg/kg/h i.v. during surgery) pigs (Deutsche Landrasse) were subjected to CPB for 2 h with 1 h of cardioplegic cardiac arrest. Systemic hemodynamics, cardiac index (CI), coronary blood flow (CBF) and left ventricular (LV) function [pressure-volume area (PVA), preload recruitable stroke work (PRSW)] were determined before and 4 h after CPB. Myocardial expression (PCR) and protein content (Western blot) of endothelial NO synthase (eNOS) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) were measured, and right coronary relaxation was assessed postmortem. All data are given as mean ± SD. Results: Preoperative plasma LDL, HDL and cholesterol did not differ between treatment groups. Compared to control, oral treatment improved post-CPB CI, CBF, first derivative of maximal LV-pressure (LVdp/dt) and PVA (p < 0.05). Significant enhancement was achieved with perioperative reloading therapy (CI: 5.2 ± 1.0 vs. 3.9 ± 1.5 l/min/m2; CBF: 76 ± 32 vs. 43 ± 8 ml/min; LVdp/dt: 1,980 ± 333 vs. 1,249 ± 461 mm Hg/s; PVA: 6,954 ± 941 vs. 3,252 ± 1,822 mm Hg·ml; p < 0.05) with improved in vitro NO-dependent coronary relaxation (102 ± 10 vs. 79 ± 14%; p = 0.003). Irrespective of recapture therapy statin pretreatment augmented myocardial eNOS and PTEN (p < 0.05), but failed to increase cardiac eNOS or PTEN expression after CPB. Conclusions: Periprocedural statin reloading therapy enhances myocardial and coronary function after cardiac surgery with CPB and may therefore provide a valuable therapeutic approach for the reduction of myocardial ischemia-reperfusion injury.

Minimally invasive direct coronary bypass grafting versus percutaneous coronary intervention for single-vessel disease: a meta-analysis of 2885 patients †

Percutaneous coronary intervention (PCI) and minimally invasive direct coronary artery bypass (MIDCAB) grafting are both established therapeutic options for single-vessel disease of the left anterior descending artery (LAD). The present systematic review with meta-analysis aims to determine the current strength of evidence for or against PCI and MIDCAB for revascularization of the LAD. Therefore, we performed a meta-analysis of randomized, controlled trials (RCTs) and observational trials (OTs) that reported clinical outcome after isolated LAD revascularization. Analysed postoperative outcomes included major adverse cardiac and cerebrovascular events (MACCEs), all-cause mortality, myocardial infarction and stroke. Pooled treatment effects [odds ratio (OR) or weighted mean difference (WMD), 95% confidence intervals (95% CI)] were assessed using a fixed- or random-effects model. A total of 2885 patients from 12 studies (6 RCTs, 6 OTs) were identified after a literature search of major databases using a predefined list of keywords. PCI of the LAD was performed in 60.7% (n = 1751) and MIDCAB in 39.3% of patients (n = 1126). Pooled-effect estimates revealed an increased incidence for MACCEs after PCI (OR 1.98; 95% CI 1.45-2.69; P < 0.0001) 6 months after the procedure. Especially, PCI was particularly associated with an increased odds for target vessel revascularization (OR 2.11; 95% CI 1.00-4.47; P = 0.0295). No differences with regard to stroke, myocardial infarction and all-cause mortality were observed between both revascularization strategies. Patients after PCI had a shorter length of hospital stay (WMD -3.37 days; 95% CI (-)4.92 to (-)1.81; P < 0.0001). In conclusion, the present systematic review underscores the superiority of MIDCAB over PCI for treatment of single-vessel disease of the LAD.

Enhanced gap junction expression in myoblast-containing engineered tissue

Transplantation of skeletal myoblasts (SMs) has been investigated as a potential cardiac cell therapy approach. SM are available autologously, predetermined for muscular differentiation and resistant to ischemia. Major hurdles for their clinical application are limitations in purity and yield during cell isolation as well as the absence of gap junction expression after differentiation into myotubes. Furthermore, transplanted SMs do not functionally or electrically integrate with the host myocardium. Here, we describe an efficient method for isolating homogeneous SM populations from neonatal mice and demonstrate persistent gap junction expression in an engineered tissue. This method resulted in a yield of 1.4 × 10(8) high-purity SMs (>99% desmin positive) after 10 days in culture from 162.12 ± 11.85 mg muscle tissue. Serum starvation conditions efficiently induced differentiation into spontaneously contracting myotubes that coincided with loss of gap junction expression. For mechanical conditioning, cells were integrated into engineered tissue constructs. SMs within tissue constructs exhibited long term survival, ordered alignment, and a preserved ability to differentiate into contractile myotubes. When the tissue constructs were subjected to passive longitudinal tensile stress, the expression of gap junction and cell adherence proteins was maintained or increased throughout differentiation. Our studies demonstrate that mechanical loading of SMs may provide for improved electromechanical integration within the myocardium, which could lead to more therapeutic opportunities.

Lactate and lactate clearance as valuable tool to evaluate ECMO therapy in cardiogenic shock

Purpose: ECMO support is an ultimate ratio therapy for patients in refractory cardiogenic shock and is linked to high mortality. We assessed the dynamic characteristics of lactate during ECMO therapy and its predictive role on 30‐day mortality. Materials and methods: Data were retrospectively collected in all patients receiving ECMO support longer than 48 h for cardiogenic shock from 01/2008 to 12/2016. Blood lactate was recorded before ECMO implantation, at prespecified timepoints during ECMO support, 1 h and 6 h post‐ECMO as well as peak lactate during ECMO and peak within 24 h after ECMO support. Statistical analysis included t‐test and ROC‐curves to identify cut‐off levels for lactate levels to predict 30‐day mortality. Results: 139 patients underwent ECMO therapy longer than 48 h for refractory cardiogenic shock resulting in a 30‐day mortality of 68%. Lactate before ECMO and peak lactate level during ECMO support showed no significant connection to mortality, while lactate and lactate clearance at 24 h were predictive for 30‐day mortality with cut‐off values of 2.15 mmol/l and 0.687 respectively. Conclusions: Dynamic course of lactate during ECMO therapy is a valuable tool to assess effective circulatory support and is superior to single lactate measurements as a predictive marker for 30‐day mortality. HighlightsECMO therapy remains an ultima ratio treatment with high mortality.Dynamic lactate behavior is valuable for assessment of effective ECMO support.Course of lactate during and after ECMO allows recognition of clinical problems.

Thrombosis of the aortic root and ascending aorta during extracorporeal membrane oxygenation

Emergent coronary artery bypass grafting was performed in a 73-year-old male patient due to an interventional left main stem coronary artery dissection. Following the operation the patient had to be put on femoral extracorporeal membrane oxygenation (ECMO) due to postcardiotomy cardiogenic shock. ECMO flow was adjusted according to measurements of the mixed venous or central venous saturation of oxygen (target 70 %; 4–4.5 l/min ECMO flow). Anticoagulation with intravenous heparin was guided by the activated clotting time (ACT), which was kept strictly above 140 s throughout the whole period of treatment resulting in partial thromboplastin time levels of between 44 and 65 s. Additionally, the thrombocyte count was between 35 and 75 Gyl throughout the whole period of treatment. A heparin-induced thrombocytopenia was ruled out by testing for platelet factor 4–heparin complexes. Three days later, after failed weaning from ECMO, echocardiography showed severe biventricular failure and thrombosis of the entire aortic root and the proximal part of the ascending aorta (Fig. 1). The patient died as a consequence of long-lasting myocardial ischemia and secondary multiple organ failure. If left ventricular output is not